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WO2012149491A3 - Recombinant microorganisms for enhanced production of mevalonate, isoprene, and isoprenoids - Google Patents

Recombinant microorganisms for enhanced production of mevalonate, isoprene, and isoprenoids Download PDF

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Publication number
WO2012149491A3
WO2012149491A3 PCT/US2012/035687 US2012035687W WO2012149491A3 WO 2012149491 A3 WO2012149491 A3 WO 2012149491A3 US 2012035687 W US2012035687 W US 2012035687W WO 2012149491 A3 WO2012149491 A3 WO 2012149491A3
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WO
WIPO (PCT)
Prior art keywords
mevalonate
isoprenoids
isoprene
production
enterococcus
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2012/035687
Other languages
French (fr)
Other versions
WO2012149491A2 (en
Inventor
Zachary Q. Beck
Michael C. Miller
Caroline M. Peres
Yuliya A. PRIMAK
Jeff P. Pucci
Derek H. Wells
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Goodyear Tire and Rubber Co
Danisco US Inc
Original Assignee
Goodyear Tire and Rubber Co
Danisco US Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Goodyear Tire and Rubber Co, Danisco US Inc filed Critical Goodyear Tire and Rubber Co
Priority to SG2013080304A priority Critical patent/SG194690A1/en
Priority to CN201280031900.1A priority patent/CN103930541A/en
Priority to BR112013027555-3A priority patent/BR112013027555A2/en
Priority to JP2014508164A priority patent/JP6301827B2/en
Priority to EP12720353.7A priority patent/EP2702140B1/en
Priority to CA2834633A priority patent/CA2834633A1/en
Priority to AU2012249320A priority patent/AU2012249320A1/en
Priority to ES12720353T priority patent/ES2699747T3/en
Publication of WO2012149491A2 publication Critical patent/WO2012149491A2/en
Publication of WO2012149491A3 publication Critical patent/WO2012149491A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C12P5/00—Preparation of hydrocarbons or halogenated hydrocarbons
    • C12P5/007—Preparation of hydrocarbons or halogenated hydrocarbons containing one or more isoprene units, i.e. terpenes
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  • Chemical & Material Sciences (AREA)
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  • General Chemical & Material Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

The invention features compositions and methods for the increased production of mevalonate, isoprene, isoprenoid precursor molecules, and/or isoprenoids in microorganisms by engineering a microorganism for increased carbon flux towards mevalonate production in the following enzymatic pathways: (a) citrate synthase, (b) phosphotransacetylase, (c) acetate kinase, (d) lactate dehydrogenase, (e) malic enzyme, and (f) pyruvate dehydrogenase such that one of more of the enzyme activity is modulated. In addition, production of mevalonate, isoprene, isoprenoid precursor molecules, and/or isoprenoids can be further enhanced by the heterologous expression of the mvaE and mvaS genes (such as, but not limited to, mvaE and mvaS genes from the organisms Listeria grayi DSM 20601, Enterococcus faecium, Enterococcus gallinarum EG2, and Enterococcus casseliflavus).
PCT/US2012/035687 2011-04-29 2012-04-27 Recombinant microorganisms for enhanced production of mevalonate, isoprene, and isoprenoids Ceased WO2012149491A2 (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
SG2013080304A SG194690A1 (en) 2011-04-29 2012-04-27 Recombinant microorganisms for enhanced production of mevalonate,isoprene, and isoprenoids
CN201280031900.1A CN103930541A (en) 2011-04-29 2012-04-27 Recombinant microorganisms for enhanced production of mevalonate, isoprene and isoprenoids
BR112013027555-3A BR112013027555A2 (en) 2011-04-29 2012-04-27 recombinant cells capable of higher production of isoprene, mevalonate and isoprenoids and method to produce isoprene, mevalonate and isoprenoids
JP2014508164A JP6301827B2 (en) 2011-04-29 2012-04-27 Recombinant microorganisms for increasing the production of mevalonic acid, isoprene and isoprenoids
EP12720353.7A EP2702140B1 (en) 2011-04-29 2012-04-27 Recombinant microorganisms for enhanced production of mevalonate, isoprene, and isoprenoids
CA2834633A CA2834633A1 (en) 2011-04-29 2012-04-27 Recombinant microorganisms for enhanced production of mevalonate, isoprene, and isoprenoids
AU2012249320A AU2012249320A1 (en) 2011-04-29 2012-04-27 Recombinant microorganisms for enhanced production of mevalonate, isoprene, and isoprenoids
ES12720353T ES2699747T3 (en) 2011-04-29 2012-04-27 Recombinant microorganisms for the enhanced production of mevalonate, isoprene and isoprenoids

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201161481121P 2011-04-29 2011-04-29
US61/481,121 2011-04-29

Publications (2)

Publication Number Publication Date
WO2012149491A2 WO2012149491A2 (en) 2012-11-01
WO2012149491A3 true WO2012149491A3 (en) 2012-12-27

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PCT/US2012/035687 Ceased WO2012149491A2 (en) 2011-04-29 2012-04-27 Recombinant microorganisms for enhanced production of mevalonate, isoprene, and isoprenoids

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US (3) US9121038B2 (en)
EP (1) EP2702140B1 (en)
JP (2) JP6301827B2 (en)
CN (1) CN103930541A (en)
AU (1) AU2012249320A1 (en)
BR (1) BR112013027555A2 (en)
CA (1) CA2834633A1 (en)
ES (1) ES2699747T3 (en)
SG (1) SG194690A1 (en)
WO (1) WO2012149491A2 (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10138498B2 (en) 2011-04-29 2018-11-27 Danisco Us Inc. Recombinant microorganisms for enhanced production of mevalonate, isoprene, and isoprenoids
US10246694B2 (en) 2013-04-10 2019-04-02 Danisco Us Inc. Phosphoketolases for improved production of acetyl coenzyme A-derived metabolites, isoprene, isoprenoid precursors, and isoprenoids

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8647642B2 (en) 2008-09-18 2014-02-11 Aviex Technologies, Llc Live bacterial vaccines resistant to carbon dioxide (CO2), acidic PH and/or osmolarity for viral infection prophylaxis or treatment
EP2794851A2 (en) * 2011-12-23 2014-10-29 Danisco US Inc. Enhanced production of isoprene using marine bacterial cells
WO2013181647A2 (en) * 2012-06-01 2013-12-05 Danisco Us Inc. Compositions and methods of producing isoprene and/or industrrial bio-products using anaerobic microorganisms
RU2723620C2 (en) * 2012-07-13 2020-06-16 Калиста, Инк. System, methods and compositions for bioprocessing
CN104540949B (en) * 2012-08-07 2018-05-29 阿迈瑞斯公司 For stablizing the method for acetyl-coacetylase derivative compound generation
MY171958A (en) * 2013-03-15 2019-11-08 Amyris Inc Use of phosphoketolase and phosphotransacetylase for production of acetyl-coenzyme a derived compounds
JP6139244B2 (en) * 2013-04-23 2017-05-31 住友ゴム工業株式会社 Polyisoprenoid production method, production agent therefor, and polyisoprenoid produced by such method
RU2013146377A (en) 2013-10-17 2015-04-27 Закрытое акционерное общество "Научно-исследовательский институт Аджиномото-Генетика" (ЗАО "АГРИ") METHOD FOR PRODUCING ISOPRENE USING BACTERIA OF THE GENUS Bacillus
US20160237442A1 (en) * 2013-10-18 2016-08-18 University Of Washington Through Its Center For Commercialization Modified group i methanotrophic bacteria and uses thereof
US20160237398A1 (en) * 2013-10-18 2016-08-18 University Of Washington Through Its Center For Commercialization Methods of microbial production of excreted products from methane and related bacterial strains
US20160376600A1 (en) 2013-11-25 2016-12-29 Genomatica, Inc. Methods for enhancing microbial production of specific length fatty alcohols in the presence of methanol
PL3077501T3 (en) 2013-12-03 2022-01-31 Genomatica, Inc. MICRO-ORGANISMS AND WAYS TO IMPROVE PRODUCT PERFORMANCE ON METHANOL WITH ACETYL-COA SYNTHESIS
CN104164457B (en) * 2014-07-15 2016-05-04 青岛农业大学 A kind of method and corresponding recombinant cell and application that utilizes the synthetic isoprene of new MVA approach
JP6470532B2 (en) * 2014-09-17 2019-02-13 積水化学工業株式会社 Recombinant cells and methods for producing organic compounds
CN104593405A (en) * 2014-11-24 2015-05-06 安徽大学 Construction method of bacillus subtilis engineering bacteria for high yield of alanine
KR101776375B1 (en) * 2015-03-18 2017-09-08 씨제이제일제당 (주) Pyruvate dehydrogenase variants, a microorganism comprising the same and a method for producing L-amino acid using the same
US10676723B2 (en) 2015-05-11 2020-06-09 David Gordon Bermudes Chimeric protein toxins for expression by therapeutic bacteria
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CN105647953A (en) * 2016-03-18 2016-06-08 黑龙江大学 Construction method of klebsiella oxytoca gene engineering strains for producing 2,3-butanediol with high yield and fermentation method of klebsiella oxytoca gene engineering strains
CN105647954A (en) * 2016-03-18 2016-06-08 黑龙江大学 Construction method of klebsiella oxytoca gene engineering strains for producing 2,3-butanediol with high yield and fermentation method of klebsiella oxytoca gene engineering strains
CN106148262B (en) * 2016-07-01 2019-09-03 江南大学 Recombinant Bacillus subtilis for improving the production of acetylglucosamine and its construction method
US11180535B1 (en) 2016-12-07 2021-11-23 David Gordon Bermudes Saccharide binding, tumor penetration, and cytotoxic antitumor chimeric peptides from therapeutic bacteria
US11129906B1 (en) 2016-12-07 2021-09-28 David Gordon Bermudes Chimeric protein toxins for expression by therapeutic bacteria
CN109234216B (en) * 2017-07-10 2022-05-20 上海医药工业研究院 Genetically engineered bacterium for producing squalene and method thereof
CN107937431A (en) * 2017-10-28 2018-04-20 国际竹藤中心 A method for improving the ability of Saccharomyces cerevisiae to synthesize linalool
CN109722403B (en) * 2017-10-30 2020-12-04 中国石油化工股份有限公司 A kind of engineering strain and method for preparing farnesene using cellulose
CN108179114B (en) * 2017-11-27 2021-08-20 南京晓庄学院 Strain producing anti-anaerobic bacteria compound and fermentation method, anti-anaerobic bacteria compound extraction and preparation method and use method
CA3084263A1 (en) 2017-12-07 2019-06-13 Zymergen Inc. Engineered biosynthetic pathways for production of (6e)-8-hydroxygeraniol by fermentation
CN111868047A (en) 2017-12-21 2020-10-30 齐默尔根公司 Nepeta hemiacetal oxidoreductase, Nepeta hemiacetal synthase, and nepetalactone-producing microorganisms
HUE065696T2 (en) 2018-03-06 2024-06-28 Danisco Us Inc Reduction in acetate production by yeast over-expressing pab1
CN110964679B (en) * 2018-09-29 2022-06-28 中国石油化工股份有限公司 Engineering strain and method for preparing farnesene by using cellulose
CN110964680B (en) * 2018-09-29 2022-06-28 中国石油化工股份有限公司 Engineering strain and method for preparing farnesene using cellulose
WO2020071538A1 (en) 2018-10-05 2020-04-09 Ajinomoto Co., Inc. Method for producing target substance by bacterial fermentation
US11845940B2 (en) * 2020-02-27 2023-12-19 The Regents Of The University Of California Genetically modified fungal cells and methods useful for producing prespatane
AU2021305200A1 (en) * 2020-07-08 2023-02-16 The Regents Of The University Of California Modified yeast host cells useful for producing isoprenol
WO2022032084A1 (en) * 2020-08-06 2022-02-10 Synlogic Operating Company, Inc. Recombinant bacteria for production of d-lactate and/or l-lactate and uses thereof
CN115704038B (en) * 2021-08-10 2025-08-15 西北农林科技大学 Gene, recombinant vector, engineering bacterium and application thereof
JP2023105728A (en) * 2022-01-19 2023-07-31 旭化成株式会社 Method for producing modified microorganisms and compounds
CN115948444A (en) * 2022-10-21 2023-04-11 江南大学 A method for improving the anaerobic activity of Bacillus licheniformis by using nitrate and the global anaerobic regulator Fnr
CN116925991B (en) * 2023-07-28 2024-08-09 天津大学 Recombinant halomonas strain for high yield of mevalonate and construction method and application thereof
CN119286752B (en) * 2024-12-10 2025-07-11 杭州合碳创物科技有限公司 Recombinant escherichia coli for producing mevalonic acid and application thereof

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000078935A1 (en) * 1999-06-22 2000-12-28 Smithkline Beecham Corporation Mevalonate pathway genes
EP1510583A1 (en) * 2002-05-10 2005-03-02 Kyowa Hakko Kogyo Co., Ltd. Process for producing mevalonic acid
WO2007140339A2 (en) * 2006-05-26 2007-12-06 Amyris Biotechnologies, Inc. Production of isoprenoids
JP2008061506A (en) * 2006-09-04 2008-03-21 Adeka Corp NEW ACETOACETYL-CoA SYNTHASE, DNA SEQUENCE ENCODING THE SAME, METHOD FOR PRODUCING THE SAME ENZYME AND METHOD FOR PRODUCING MEVALONIC ACID UTILIZING THE SAME ENZYME
WO2009076676A2 (en) * 2007-12-13 2009-06-18 Danisco Us Inc. Compositions and methods for producing isoprene
WO2010031077A1 (en) * 2008-09-15 2010-03-18 Danisco Us Inc. Increased isoprene production using mevalonate kinase and isoprene synthase
WO2010078457A2 (en) * 2008-12-30 2010-07-08 Danisco Us Inc. Methods of producing isoprene and a co-product
WO2010148150A1 (en) * 2009-06-17 2010-12-23 Danisco Us Inc. Improved isoprene production using the dxp and mva pathway
WO2010148256A1 (en) * 2009-06-17 2010-12-23 Danisco Us Inc. Fuel compositions comprising isoprene derivatives
WO2011079314A2 (en) * 2009-12-23 2011-06-30 Danisco Us Inc. Compositions and methods of pgl for the increased production of isoprene

Family Cites Families (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19629568C1 (en) 1996-07-15 1998-01-08 Fraunhofer Ges Forschung Process for the production of isoprene
US7172886B2 (en) 2001-12-06 2007-02-06 The Regents Of The University Of California Biosynthesis of isopentenyl pyrophosphate
AU2003287028B2 (en) 2002-10-04 2008-09-04 E.I. Du Pont De Nemours And Company Process for the biological production of 1,3-propanediol with high yield
JP4168870B2 (en) * 2003-08-14 2008-10-22 トヨタ自動車株式会社 Method for producing prenyl alcohol
RU2004124226A (en) 2004-08-10 2006-01-27 Закрытое акционерное общество "Научно-исследовательский институт Аджиномото-Генетика" (ЗАО АГРИ) (RU) USE OF PHOSPHOCETHOLASE FOR PRODUCTION OF USEFUL METABOLITES
US7947478B2 (en) 2006-06-29 2011-05-24 The Regents Of The University Of California Short chain volatile hydrocarbon production using genetically engineered microalgae, cyanobacteria or bacteria
MX2009004221A (en) * 2006-10-20 2009-09-10 Univ Arizona State Modified cyanobacteria.
US7947483B2 (en) * 2007-08-10 2011-05-24 Genomatica, Inc. Methods and organisms for the growth-coupled production of 1,4-butanediol
WO2009100231A2 (en) 2008-02-06 2009-08-13 The Regents Of The University Of California Short chain volatile isoprene hydrocarbon production using the mevalonic acid pathway in genetically engineered yeast and fungi
CN102015995B (en) * 2008-03-03 2014-10-22 焦耳无限科技公司 Carbon-dioxide-fixing engineered microorganisms that produce carbon-based products of interest
JP2011518564A (en) 2008-04-23 2011-06-30 ダニスコ・ユーエス・インク Isoprene synthase mutants for isoprene production by improved microorganisms
US7632995B2 (en) 2008-05-09 2009-12-15 Monsanto Technology Llc Plants and seeds of hybrid corn variety CH852179
US10100334B2 (en) * 2008-05-23 2018-10-16 Nucelis Inc. Production of squalene using yeast
EP2310490B1 (en) 2008-07-02 2019-01-02 Danisco US Inc. Methods for producing isoprene
HU3516U (en) 2008-07-31 2008-11-28 Zoltan Kuthi Anti-theft protection of draining for fuel tanks
MY156562A (en) 2008-09-15 2016-02-26 Danisco Us Inc Increased isoprene production using the archaeal lower mevalonate pathway
WO2010031079A1 (en) 2008-09-15 2010-03-18 Danisco Us Inc. Systems using cell culture for production of isoprene
CA2737223A1 (en) 2008-09-15 2010-03-18 Danisco Us Inc. Reduction of carbon dioxide emission during isoprene production by fermentation
BRPI0918936A2 (en) 2008-09-15 2019-09-24 Danisco Us Inc conversion of prenyl derivatives to isoprene
US20100297749A1 (en) 2009-04-21 2010-11-25 Sapphire Energy, Inc. Methods and systems for biofuel production
EP2421966A2 (en) 2009-04-23 2012-02-29 Danisco US Inc. Three-dimensional structure of isoprene synthase and its use thereof for generating variants
JP4760951B2 (en) 2009-05-08 2011-08-31 トヨタ自動車株式会社 Recombinant microorganism having butanol-producing ability and method for producing butanol
CA2773675A1 (en) 2009-09-15 2011-03-24 Sapphire Energy, Inc. A system for transformation of the chloroplast genome of scenedesmus sp. and dunaliella sp.
JP5978132B2 (en) * 2009-11-23 2016-08-24 ニューセリス インコーポレイテッド Methods and compositions for squalene production using yeast
CN102884028B (en) 2009-12-18 2015-08-19 丹尼斯科美国公司 Purification of isoprene from renewable resources
WO2012019169A1 (en) * 2010-08-06 2012-02-09 Danisco Us Inc. Production of isoprene under neutral ph conditions
JP2014502148A (en) 2010-10-27 2014-01-30 ダニスコ・ユーエス・インク Isoprene synthase mutants aimed at improving isoprene production
EP2655606A1 (en) * 2010-12-22 2013-10-30 Danisco US Inc. Compositions and methods for improved isoprene production using two types of ispg enzymes
US9121038B2 (en) 2011-04-29 2015-09-01 The Goodyear Tire & Rubber Company Recombinant microorganisms for enhanced production of mevalonate, isoprene, and isoprenoids
JP2014519811A (en) * 2011-04-29 2014-08-21 ダニスコ・ユーエス・インク Production of mevalonate, isoprene, and isoprenoids using genes encoding polypeptides having thiolase, HMG-CoA synthase and HMG-CoA reductase activity

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000078935A1 (en) * 1999-06-22 2000-12-28 Smithkline Beecham Corporation Mevalonate pathway genes
EP1510583A1 (en) * 2002-05-10 2005-03-02 Kyowa Hakko Kogyo Co., Ltd. Process for producing mevalonic acid
WO2007140339A2 (en) * 2006-05-26 2007-12-06 Amyris Biotechnologies, Inc. Production of isoprenoids
JP2008061506A (en) * 2006-09-04 2008-03-21 Adeka Corp NEW ACETOACETYL-CoA SYNTHASE, DNA SEQUENCE ENCODING THE SAME, METHOD FOR PRODUCING THE SAME ENZYME AND METHOD FOR PRODUCING MEVALONIC ACID UTILIZING THE SAME ENZYME
WO2009076676A2 (en) * 2007-12-13 2009-06-18 Danisco Us Inc. Compositions and methods for producing isoprene
WO2010031077A1 (en) * 2008-09-15 2010-03-18 Danisco Us Inc. Increased isoprene production using mevalonate kinase and isoprene synthase
WO2010078457A2 (en) * 2008-12-30 2010-07-08 Danisco Us Inc. Methods of producing isoprene and a co-product
WO2010148150A1 (en) * 2009-06-17 2010-12-23 Danisco Us Inc. Improved isoprene production using the dxp and mva pathway
WO2010148256A1 (en) * 2009-06-17 2010-12-23 Danisco Us Inc. Fuel compositions comprising isoprene derivatives
WO2011079314A2 (en) * 2009-12-23 2011-06-30 Danisco Us Inc. Compositions and methods of pgl for the increased production of isoprene

Non-Patent Citations (10)

* Cited by examiner, † Cited by third party
Title
HEMMI H ET AL: "IDENTIFICATION OF GENES AFFECTING LYCOPENE FORMATION IN ESCHERICHIA COLI TRANSFORMED WITH CAROTENOID BIOSYNTHETIC GENES: CANDIDATES FOR EARLY GENES IN ISOPRENOID BIOSYNTHESIS", JOURNAL OF BIOCHEMISTRY, vol. 123, no. 6, 1 June 1998 (1998-06-01), pages 1088 - 1096, XP001161200, ISSN: 0021-924X *
HISASHI HARADA ET AL: "Novel approaches and achievements in biosynthesis of functional isoprenoids in Escherichia coli", APPLIED MICROBIOLOGY AND BIOTECHNOLOGY, vol. 84, no. 6, 12 August 2009 (2009-08-12), pages 1021 - 1031, XP019757474, ISSN: 1432-0614 *
KAZUHIKO TABATA ET AL: "Production of mevalonate by a metabolically-engineered Escherichia coli", BIOTECHNOLOGY LETTERS, vol. 26, no. 19, 1 October 2004 (2004-10-01), pages 1487 - 1491, XP055013815, ISSN: 0141-5492 *
MIZIORKO ET AL: "Enzymes of the mevalonate pathway of isoprenoid biosynthesis", ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, vol. 505, no. 2, 15 January 2011 (2011-01-15), pages 131 - 143, XP027587651, ISSN: 0003-9861 *
PITERA ET AL: "Balancing a heterologous mevalonate pathway for improved isoprenoid production in Escherichia coli", METABOLIC ENGINEERING, vol. 9, no. 2, 16 February 2007 (2007-02-16), pages 193 - 207, XP005888126, ISSN: 1096-7176 *
R.V. VADALI ET AL: "Enhanced Lycopene Productivity by Manipulation of Carbon Flow to Isopentenyl Diphosphate in Escherichia coli", BIOTECHNOLOGY PROGRESS, vol. 21, no. 5, 7 October 2005 (2005-10-07), pages 1558 - 1561, XP055035831, ISSN: 8756-7938 *
SUZANNE M MA ET AL: "Optimization of a heterologous mevalonate pathway through the use of variant HMG-CoA reductases", METABOLIC ENGINEERING, vol. 13, no. 5, 13 July 2011 (2011-07-13), pages 588 - 597, XP028274826, ISSN: 1096-7176 *
TAO L ET AL: "Isolation of chromosomal mutations that affect carotenoid production in Escherichia coli: mutations alter copy number of ColE1-type plasmids", FEMS MICROBIOLOGY LETTERS, vol. 243, no. 1, 1 February 2005 (2005-02-01), pages 227 - 233, XP027871619, ISSN: 0378-1097 *
W.R. FARMER ET AL: "Precursor Balancing for Metabolic Engineering of Lycopene Production in Escherichia coli", BIOTECHNOLOGY PROGRESS, vol. 17, no. 1, 2 February 2001 (2001-02-02), pages 57 - 61, XP055035828, ISSN: 8756-7938 *
WILDING E I ET AL: "Identification, evolution, and essentiality of the mevalonate pathway for isopentenyl diphosphate biosynthesis in gram-positive cocci", JOURNAL OF BACTERIOLOGY, vol. 182, no. 15, 1 August 2000 (2000-08-01), pages 4319 - 4327, XP002232852, ISSN: 0021-9193 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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US10975394B2 (en) 2011-04-29 2021-04-13 Danisco Us Inc. Recombinant microorganisms for enhanced production of mevalonate, isoprene, and isoprenoids
US10246694B2 (en) 2013-04-10 2019-04-02 Danisco Us Inc. Phosphoketolases for improved production of acetyl coenzyme A-derived metabolites, isoprene, isoprenoid precursors, and isoprenoids
US11371035B2 (en) 2013-04-10 2022-06-28 Danisco Us Inc. Phosphoketolases for improved production of acetyl coenzyme A-derived metabolites, isoprene, isoprenoid precursors, and isoprenoid

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